Reductie van cardiovasculaire gebeurtenissen door behandeling met ramipril, maar niet door behandeling met [alpha]-tocoferol bij patiënten met verhoogd risico; een gerandomiseerd, dubbelblind onderzoek

To assess the effects of ramipril and of α-tocopherol on the incidence of vascular events in subjects with a high risk of cardiovascular events.

Design

Prospective, randomized, placebo-controlled, double-blind.

Method

Between December 1993 and June 1995, 9541 patients over 55 years of age in 267 centres in Canada, North and South America and Europe were included in the trial. They were known to have overt cardiovascular disease (coronary or peripheral artery disease, previous cerebrovascular accident), or suffered from diabetes mellitus, with at least one additional cardiovascular risk factor. They were randomized according to treatment with ramipril 10 mg once daily versus placebo and within these groups they were randomized to either α-tocopherol (400 IU per day) or placebo. Data on cardiovascular events, use of medicines and side effects were collected at outpatient visits after one month, six months and then every six months. Follow-up lasted to June 1999.

Results

Of the participants, almost 27 were women and 55 were older than 65 years. Of the subjects treated with ramipril 651 (14.0) sustained a myocardial infarction or stroke, or died from cardiovascular causes, and 826 (17.8) in the placebo group (relative risk reduction 22; p < 0.001). A statistically significant reduction was observed of total mortality, of the number of patients needing a revascularisation procedure, of the number of patients with worsening of angina or who developed congestive heart failure. The number of patients developing diabetes-related complications was also reduced. This beneficial effect of ramipril was observed in all subgroups, i.e. patients with or without diabetes, men and women, patients with or without cardiovascular disease, those younger and older than 65 years, and subjects with and without hypertension. Treatment with α-tocopherol had no effect on cardiovascular morbidity or mortality.

Conclusion

In patients with an enhanced risk of cardiovascular events, ramipril reduced the probability of death, myocardial infarction or stroke whereas α-tocopherol did not.